Newly Diagnosed Carney Complex in 3 Young Adults with Primary Adrenal Cushing Syndrome – A Case Series and Review of the Literature

Objective: Carney complex (CNC) is a very rare cause of adrenocorticotropic hormone (ACTH)-independent Cushing syndrome (CS). We describe 3 cases of CNC diagnosed through the evaluation of CS, with no other major manifestations of CNC. Methods: We present the relevant history, laboratory, and pathologic data of the current cases, and review relevant documentation from the literature. Results: Among all 3 patients, CS symptomatology was the main clinical characteristic, which was also supported by a diminished diurnal rhythmicity of plasma cortisol and ACTH levels. The paradoxical increase in cortisol after both low and high dose dexamethasone suppression tests (Liddle's test) proved to be the most useful biochemical clue for the diagnosis of primary pigmented nodular adrenocortical disease (PPNAD) in these patients. The absence of bilateral macronodular or unilateral adrenal lesion led to the possible diagnosis of PPNAD/CNC. None of the 3 patients demonstrated any of the other described major manifestations of CNC. Pathologic examination confirmed PPNAD, and genetic testing showed mutations in the protein kinase A regulatory subunit type Iα gene in 2 of the 3 patients. Conclusion: CNC should be suspected among patients with micronodular primary adrenal CS, even in the absence of other major manifestations of this rare disease, as early recognition of CNC is of paramount importance for avoiding the complications from its comorbidities. Abbreviations: ACTH adrenocorticotropic hormone; CNC Carney complex; CS Cushing syndrome; IGF-1 insulin-like growth factor 1; MRI magnetic resonance imaging; PPNAD primary pigmented nodular adrenocortical disease; PRKAR1A protein kinase A regulatory subunit type Iα